title: On rat renal aminolevulinate transport and metabolism in experimental Fanconi syndrome.
abstract: Hereditary tyrosinemia, an autosomal recessive disease of human infants, is characterized by severe liver disease, a renal Fanconi syndrome, and urinary excretion of large quantities of both aminolevulinate (ALA) and succinylacetone (SA). The latter is a metabolic end-product of tyrosine catabolism in affected individuals, produced by both liver and kidney, and is a potent inhibitor of aminolevulinate dehydratase (ALAD) in liver. This inhibition has been assumed to result in release of large amounts of aminolevulinate from liver into the circulation, with subsequent urinary excretion. In the present report we examine the effects of succinylacetone on rat renal cortical tubular handling of ALA and the relationship to tubular heme content, demonstrating a marked impairment of each. In contrast, maleic acid was found to have no effect on either renal ALAD or heme content. Thus, we conclude that renal handling of ALA in SA-treated rat renal cortex may indicate a contribution by the kidney to the increased net ALA excretion observed in hereditary tyrosinemia.
authors.affiliation: Department of Pediatrics, Medical College of Virginia, Richmond 23298.
authors.forename: K S
authors.initials: KS
authors.lastname: Roth
authors.forename: B E
authors.initials: BE
authors.lastname: Carter
authors.forename: L C
authors.initials: LC
authors.lastname: Moses
authors.forename: P D
authors.initials: PD
authors.lastname: Spencer
mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000378:metabolism; D000622:Aminolevulinic Acid / Q000378:metabolism*; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D005198:Fanconi Syndrome / Q000378:metabolism*; D006418:Heme / Q000378:metabolism; D006537:Heptanoates / Q000494:pharmacology; D066298:In Vitro Techniques; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008298:Maleates / Q000494:pharmacology; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism; D000623:Porphobilinogen Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D011919:Rats, Inbred Strains; D014443:Tyrosine / Q000097:blood
chemical_list: D006537:Heptanoates; D008298:Maleates; D014443:Tyrosine; D006418:Heme; C020804:succinylacetone; D000622:Aminolevulinic Acid; C030272:maleic acid; D000623:Porphobilinogen Synthase